DESCRIPTION (Adapted from applicant's abstract and specific aims): Interleukin-8 (IL-8) is a potent neutrophil attractant and activator. IL-8 has been reported to be involved in the pathogenesis of several diseases including idiopathic dilated cardiomyopathy, sepsis, rheumatoid arthritis, psoriasis and the acute respiratory distress syndrome (ARDS). ARDS affects more than 150,000 people each year in the USA, and the mortality of severe cases remains at 50-80 percent of autoantibodies to IL-8 in lung fluids from patients with ARDS. The purpose of this research is to test two hypotheses: HYPOTHESIS 1: IL-8 function in the lung is regulated by IL-8-binding proteins, including alpha-2-macroglobulin and anti-IL-8 autoantibodies. HYPOTHESIS 2: Interaction between IL-8 and IL-8-binding proteins affects the outcome of IL-8-dependent lung inflammation. The specific aims are: 1a) to determine how alpha-2-macroglobulin affects IL-8 function in the lung; 1b) to determine if the autoantibodies to IL-8 modulate IL-8 activity in the lung; 2a) to determine if antibodies against IL-8 prevent the development of IL-8-dependent lung inflammation in rabbits; 2b) to establish if alpha-macroglobulin affects the course of IL-8-dependent lung inflammation in rabbits; 2c) to determine if antibodies to IL-8 and alpha-macroglobulin act in synergy to regulate IL-8 in vivo; and 2d) to establish if the presence of alpha-2-macroglobulin and anti-IL-8 autoantibodies at different stages of the acute lung injury correlates with the improved survival rate in patients with ARDS.